Journal of Orthopaedic Translation最新文献

{"title":"Corrigendum to ‘YAP maintains cartilage stem/progenitor cell homeostasis in osteoarthritis’[Journal of Orthopaedic Translation 46 (2024) 79–90]","authors":"Lina Zhang , Xinxing Wang , Guang Xia , Junjie Huang , Zi Wen , Chi Liang , Xu Cao , Yong Zhou , Song Wu","doi":"10.1016/j.jot.2024.08.021","DOIUrl":"10.1016/j.jot.2024.08.021","url":null,"abstract":"","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Page 341"},"PeriodicalIF":5.9,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11681330/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142903089","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mesoporous bioactive glass-enhanced MSC-derived exosomes promote bone regeneration and immunomodulation in vitro and in vivo","authors":"Qingde Wa ,&nbsp;Yongxiang Luo ,&nbsp;Yubo Tang ,&nbsp;Jiaxiang Song ,&nbsp;Penghui Zhang ,&nbsp;Xitao Linghu ,&nbsp;Sien Lin ,&nbsp;Gang Li ,&nbsp;Yixiao Wang ,&nbsp;Zhenyu Wen ,&nbsp;Shuai Huang ,&nbsp;Weikang Xu","doi":"10.1016/j.jot.2024.09.009","DOIUrl":"10.1016/j.jot.2024.09.009","url":null,"abstract":"<div><h3>Background</h3><div>Exosomes produced by mesenchymal stem cells (MSCs) have vascular generative properties and are considered new effective candidates for the treatment of bone defects as alternatives to cell therapy. Improving the pro-regenerative function and efficacy of exosomes has been a popular research topic in the field of orthopaedics.</div></div><div><h3>Methods</h3><div>We prepared mesoporous bioactive glass (mBG) microspheres via the template method. The ionic products of mBGs used to treat MSCs were extracted, and the effects of exosomes secreted by MSCs on osteoblast (OB) and macrophage (MP) behaviour and bone defect repair were observed in vivo (Micro-CT, H&amp;E, Masson, and immunofluorescence staining for BMP2, COL1, VEGF, CD31, CD163, and iNOS).</div></div><div><h3>Results</h3><div>The mBG spheres were successfully prepared, and the Exo-mBG were isolated and extracted. Compared with those in the blank and Exo-Con groups, the proliferation and osteogenic differentiation of OBs in the Exo-mBG group were significantly greater. For example, on Day 7, OPN gene expression in the Ctrl-Exo group was 3.97 and 2.83 times greater than that in the blank and Exo-mBG groups, respectively. In a cranial defect rat model, Exo-mBG promoted bone tissue healing and angiogenesis, increased M2 macrophage polarisation and inhibited M1 macrophage polarisation, as verified by micro-CT, H&amp;E staining, Masson staining and immunofluorescence staining. These effects may be due to the combination of a higher silicon concentration and a higher calcium-to-phosphorus ratio in the mBG ionic products.</div></div><div><h3>Conclusion</h3><div>This study provides insights for the application of exosomes in cell-free therapy and a new scientific basis and technical approach for the utilisation of MSC-derived exosomes in bone defect repair.</div></div><div><h3>The translational potential of this article</h3><div>Our study demonstrated that exosomes produced by mBG-stimulated MSCs have excellent in vitro and in vivo bone-enabling and immunomodulatory functions and provides insights into the use of exosomes in clinical cell-free therapies.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 264-282"},"PeriodicalIF":5.9,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142539564","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineered melatonin-pretreated plasma exosomes repair traumatic spinal cord injury by regulating miR-138-5p/SOX4 axis mediated microglia polarization","authors":"Hao Chen ,&nbsp;Huihui Sun ,&nbsp;Yaqing Yang ,&nbsp;Pingchuan Wang ,&nbsp;Xizhao Chen ,&nbsp;Junxiang Yin ,&nbsp;Aoying Li ,&nbsp;Liang Zhang ,&nbsp;Jun Cai ,&nbsp;Jijun Huang ,&nbsp;Shengfei Zhang ,&nbsp;Zhiqiang Zhang ,&nbsp;Xinmin Feng ,&nbsp;Jian Yin ,&nbsp;Yongxiang Wang ,&nbsp;Wu Xiong ,&nbsp;Bowen Wan","doi":"10.1016/j.jot.2024.09.007","DOIUrl":"10.1016/j.jot.2024.09.007","url":null,"abstract":"<div><h3>Background</h3><div>Neuroinflammation plays a crucial role in the repair of spinal cord injury (SCI), with microglia, pivotal in neuroinflammation, driving either degeneration or recovery in this pathological process. Recently, plasma-derived exosomes (denoted Exos) have presented a high capacity for promoting functional recovery of SCI through the anti-inflammatory effects, and pretreated exosomes are associated with better outcomes. Thus, we aimed to explore whether melatonin-pretreated plasma-derived exosomes (denoted MExo) could exert superior effects on SCI, and attempted to elucidate the potential mechanisms.</div></div><div><h3>Methods</h3><div>Electron microscopy, nanoparticle tracking analysis, and western blot were applied to delineate the distinctions between Exos and MExos. To assess their therapeutic potentials, we established a contusion SCI rat model, complemented by a battery of in vitro experiments comparing both groups. Subsequently, a miRNA microarray analysis was conducted, followed by a series of rescue experiments to elucidate the specific role of miRNAs in MExos. To further delve into the molecular mechanisms involved, we employed western blot analysis and the luciferase reporter gene assay.</div></div><div><h3>Results</h3><div>Melatonin promoted the release of exosome from plasma, concurrently amplifying their anti-inflammatory properties. Furthermore, it was discerned that MExos facilitated a transition in microglia polarization from M1 to M2 phenotype, a phenomenon more pronounced than that observed with Exos. In an endeavor to elucidate this variance, we scrutinized miRNAs exhibiting elevated expression levels in MExos, pinpointing miR-138-5p as a pivotal element in this dynamic. Following this, an in-depth investigation into the role of miR-138-5p was undertaken, which uncovered its efficacy in driving phenotypic alterations within microglia. The analysis of downstream genes targeted by miR-138-5p revealed that it exerted a negative regulatory influence on SOX4, which was found to obstruct the generation of M2-type microglia and the secretion of anti-inflammatory cytokines, thereby partially elucidating the mechanism behind miR-138-5p′s regulation of microglia polarization.</div></div><div><h3>Conclusions</h3><div>We innovatively observed that melatonin enhanced the anti-inflammatory function of Exos, which further decreased the expression of SOX4 by delivering miR-138-5p. This inhibition promoted the conversion of M1 microglia to M2 microglia, thus offering a viable option for the treatment of SCI.</div></div><div><h3>The translational potential of this article</h3><div>This study highlights that melatonin enhances the anti-inflammatory function of Exos through delivery of miR-138-5p. Activation of miR-138-5p/SOX4 axis by engineered melatonin-pretreated plasma exosomes may be a potential target for SCI treatment.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 230-245"},"PeriodicalIF":5.9,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Engineering natural DNA matrices with halloysite nanotubes to fabricate injectable therapeutic hydrogels for bone regeneration","authors":"Yali Miao ,&nbsp;Teliang Lu ,&nbsp;Shangbin Cui ,&nbsp;Ziyang Xu ,&nbsp;Xiao Liu ,&nbsp;Yu Zhang","doi":"10.1016/j.jot.2024.09.010","DOIUrl":"10.1016/j.jot.2024.09.010","url":null,"abstract":"<div><h3>Background</h3><div>Injectable hydrogels are widely used in drug delivery and the repair of irregular tissue defects due to their advantages such as convenient and minimally invasive operation. Although the existing injectable hydrogels have excellent biocompatibility and osteoconduction, they still face clinical challenges such as low osteogenic activity. The key requirements for improved injectable hydrogels as repair materials for non-load bearing bone defects are optimal handling properties, the ability to fill irregular defects and provide osteoinductive stimulation.</div></div><div><h3>Methods</h3><div>We developed an approach to construct injectable hydrogels through a two-step gelation process. In the first step of gelation, the denaturation and rehybridization mechanism of natural biopolymer DNA was utilized to form interconnected structure through hydrogen bonding between complementary base pairs between the DNA strands. In the second step of gelation, the introduction of halloysite nanotubes (HNTs) loaded with osteogenic model drug dexamethasone (Dex) provided additional crosslinking sites through non-covalent interactions with the DNA backbone, including electrostatic interaction and hydrogen bonding interaction.</div></div><div><h3>Results</h3><div>The DNA-based nanocomposite hydrogel material developed in our work can be used as an injectable filling material for the repair of non-load bearing bone defect and can be loaded with osteogenic model drug dexamethasone (Dex) for improved osteoinductivity, promoting new bone regeneration <em>in vivo</em>.</div></div><div><h3>Translational potential of this article</h3><div>This article highlights the potential of using nanocomposite hydrogels to repair non-load bearing bone defects, which are common injuries in the clinic. This study provides a deeper understanding of how to optimize the properties of hydrogels to regulate cell differentiation and tissue formation.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 218-229"},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"IHH–GLI-1–HIF-2α signalling influences hypertrophic chondrocytes to exacerbate osteoarthritis progression","authors":"Chengming Zhang ,&nbsp;Ruipeng Zhao ,&nbsp;Zhengquan Dong ,&nbsp;Yang Liu ,&nbsp;Mengrou Liu ,&nbsp;Haoqian Li ,&nbsp;Yukun Yin ,&nbsp;Xianda Che ,&nbsp;Gaige Wu ,&nbsp;li Guo ,&nbsp;Pengcui Li ,&nbsp;Xiaochun Wei ,&nbsp;Ziquan Yang","doi":"10.1016/j.jot.2024.09.008","DOIUrl":"10.1016/j.jot.2024.09.008","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Chondrocyte hypertrophy is a potential target for osteoarthritis (OA) treatment, with Indian hedgehog (IHH), glioma-associated oncogene homolog (GLI), and hypoxia-inducible factor-2α (HIF-2α) being closely associated with chondrocyte hypertrophy during OA progression. Whereas IHH can modulate chondrocyte hypertrophy, interference with IHH signalling has not achieved the anticipated therapeutic effects and poses safety concerns, necessitating further clarification of the specific mechanisms by which IHH affects articular cartilage degeneration. Inhibition of the HIF-2α overexpression in cartilage slows the progression of early OA, but the mechanisms underlying HIF-2α accumulation in OA cartilage remain unclear. The aim of this study was to determine the function of Ihh, as well as its downstream factors, in chondrocytes, based on an early osteoarthritis (OA) mouse model and in vitro chondrocyte model.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Methods&lt;/h3&gt;&lt;div&gt;Investigated the expression levels and locations of IHH–GLI-1 pathway in normal and early degenerated human cartilage, comparing them with HIF-2α and its downstream factors. RT-qPCR, Western blotting, Crystal violet staining, and EdU assays were used to evaluate the pecific regulatory mechanisms of the IHH–GLI-1–HIF-2α signalling axis in normal chondrocytes and in chondrocytes under inflammatory conditions. Validated the impact of IHH on early cartilage degeneration and the relationship between the IHH-GLI-1 pathway and the expression levels and expression locations of HIF-2α and its downstream factors in Col2a1-Cre&lt;sup&gt;ERT2&lt;/sup&gt;;Ihh&lt;sup&gt;fl/fl&lt;/sup&gt; mice.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Results&lt;/h3&gt;&lt;div&gt;In early-stage degenerative joint cartilage, the GLI-1 pathway in hypertrophic chondrocytes exhibited similar changes in location and levels to HIF-2α and its downstream factor vascular endothelial growth factor (VEGF). In vitro, IHH–GLI-1–HIF-2α signalling activation in chondrocytes under physiological hypoxic conditions inhibited chondrocyte proliferation. In chondrocytes stimulated by inflammatory environments, IHH inhibited the degradation of HIF-2α via the GLI-1 pathway, thereby promoting HIF-2α protein expression. Elevated HIF-2α expression further enhanced intracellular IHH–GLI-1 levels, generating a positive feedback loop to collectively regulate the expression of downstream hypertrophic factors and matrix-degradation factors. &lt;em&gt;In vivo&lt;/em&gt;, conditional &lt;em&gt;Ihh&lt;/em&gt; knockout in mouse chondrocytes downregulated Hif-2α protein expression in early degenerative cartilage tissue and affected the expression of downstream Vegf and hypertrophic factors.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Conclusions&lt;/h3&gt;&lt;div&gt;During OA progression, the IHH–GLI-1–HIF-2α axis mainly operates within hypertrophic chondrocytes, exacerbating cartilage degeneration by regulating hypertrophic chondrocyte functions, cartilage matrix degradation, and microvascular invasion.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 207-217"},"PeriodicalIF":5.9,"publicationDate":"2024-10-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142526263","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Role of oxidative stress in mitochondrial dysfunction and their implications in intervertebral disc degeneration: Mechanisms and therapeutic strategies","authors":"Hao Zhou ,&nbsp;Chenyu Wu ,&nbsp;Yuxin Jin ,&nbsp;Ouqiang Wu ,&nbsp;Linjie Chen ,&nbsp;Zhenyu Guo ,&nbsp;Xinzhou Wang ,&nbsp;Qizhu Chen ,&nbsp;Kenny Yat Hong Kwan ,&nbsp;Yan Michael Li ,&nbsp;Dongdong Xia ,&nbsp;Tao Chen ,&nbsp;Aimin Wu","doi":"10.1016/j.jot.2024.08.016","DOIUrl":"10.1016/j.jot.2024.08.016","url":null,"abstract":"&lt;div&gt;&lt;h3&gt;Background&lt;/h3&gt;&lt;div&gt;Intervertebral disc degeneration (IVDD) is widely recognized as one of the leading causes of low back pain. Intervertebral disc cells are the main components of the intervertebral disc (IVD), and their functions include synthesizing and secreting collagen and proteoglycans to maintain the structural and functional stability of the IVD. In addition, IVD cells are involved in several physiological processes. They help maintain nutrient metabolism balance in the IVD. They also have antioxidant and anti-inflammatory effects. Because of these roles, IVD cells are crucial in IVDD. When IVD cells are subjected to oxidative stress, mitochondria may become damaged, affecting normal cell function and accelerating degenerative changes. Mitochondria are the energy source of the cell and regulate important intracellular processes. As a key site for redox reactions, excessive oxidative stress and reactive oxygen species can damage mitochondria, leading to inflammation, DNA damage, and apoptosis, thus accelerating disc degeneration.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Aim of review&lt;/h3&gt;&lt;div&gt;Describes the core knowledge of IVDD and oxidative stress. Comprehensively examines the complex relationship and potential mechanistic pathways between oxidative stress, mitochondrial dysfunction and IVDD. Highlights potential therapeutic targets and frontier therapeutic concepts. Draws researchers' attention and discussion on the future research of all three.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;Key scientific concepts of review&lt;/h3&gt;&lt;div&gt;Origin, development and consequences of IVDD, molecular mechanisms of oxidative stress acting on mitochondria, mechanisms of oxidative stress damage to IVD cells, therapeutic potential of targeting mitochondria to alleviate oxidative stress in IVDD.&lt;/div&gt;&lt;/div&gt;&lt;div&gt;&lt;h3&gt;The translational potential of this article&lt;/h3&gt;&lt;div&gt;Targeted therapeutic strategies for oxidative stress and mitochondrial dysfunction are particularly critical in the treatment of IVDD. Using antioxidants and specific mitochondrial therapeutic agents can help reduce symptoms and pain. This approach is expected to significantly improve the quality of life for patients. Individualized therapeutic approaches, on the other hand, are based on an in-depth assessment of the patient's degree of oxidative stress and mitochondrial functional status to develop a targeted treatment plan for more precise and effective IVDD management. Additionally, we suggest preventive measures like customized lifestyle changes and medications. These are based on understanding how IVDD develops. The aim is to slow down the disease and reduce the chances of it coming back. Actively promoting clinical trials and evaluating the safety and efficacy of new therapies helps translate cutting-edge treatment concepts into clinical practice. These measures not only improve patient outcomes and quality of life but also reduce the consumption of healthcare resources and the socio-economic burden, thus having a positiv","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 181-206"},"PeriodicalIF":5.9,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142442735","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A biodegradable magnesium phosphate cement incorporating chitosan and rhBMP-2 designed for bone defect repair","authors":"Peng He ,&nbsp;Yanbin Zhao ,&nbsp;Bin Wang ,&nbsp;Guoyin Liu ,&nbsp;Lei Zhang ,&nbsp;Mei Li ,&nbsp;Bin Xu ,&nbsp;Weihua Cai ,&nbsp;Chenglin Chu ,&nbsp;Yu Cong","doi":"10.1016/j.jot.2024.08.004","DOIUrl":"10.1016/j.jot.2024.08.004","url":null,"abstract":"<div><h3>Background</h3><div>The repair of bone defects has always been a significant challenge in clinical medicine. To address this challenge, doctors often utilize autologous bone grafts, allogeneic bone grafts and artificial bone substitutes. However, the former two methods may result in additional trauma and complications, while allogeneic bone grafts carry the risks of immune rejection and disease transmission. Magnesium phosphate cement (MPC), as a artificial bone substitutes, has been a potential biomaterial for repairing bone defects, but its clinical application is limited by insufficient mechanical strength and poor osteoinductive activity.</div></div><div><h3>Methods</h3><div>In this study, the cement liquid phase base on rhBMP-2 and chitosan solution into MPC were obtained and investigated. After mixing with a cement liquid, the structural and phase composition, morphology, chemical structure, setting time, compressive strength, degradation behavior, solubility, and cellular responses and bone regeneration in response to CHI-rhBMP2 MPC were investigated in vitro and in vivo.</div></div><div><h3>Results</h3><div>After the chemical component modification, CHI-rhBMP2 MPC possessed controllable degradation rate, moderate setting time, appropriate cuing temperature, good injectability, and improved initial strength. In vitro tests showed that the CHIrhBMP2 MPC could promote cell proliferation and adhesion, as well as that contribute to osteoblast differentiation and mineralization. In addition, cement materials were implanted into the rabbit femoral condyles for in vivo osseointegration evaluation. The results displayed that more new bone grew around CHI-rhBMP2 MPC, verifying improved osseointegration capacity. Transcriptome analysis revealed that focal adhesion, Forkhead box O（FoxO） signaling pathway and P13K/AKT signaling pathway were may involved in CHI-rhBMP2 MPC induced new bone formation.</div></div><div><h3>Conclusion</h3><div>This work provides a new strategy for the rational design of potential bone repair candidate materials.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 167-180"},"PeriodicalIF":5.9,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ubiquitination and deubiquitination: Implications for the pathogenesis and treatment of osteoarthritis","authors":"Shibo Su ,&nbsp;Ruijiao Tian ,&nbsp;Yang Jiao ,&nbsp;Shudan Zheng ,&nbsp;Siqiang Liang ,&nbsp;Tianyi Liu ,&nbsp;Ziheng Tian ,&nbsp;Xiuhong Cao ,&nbsp;Yanlong Xing ,&nbsp;Chuqing Ma ,&nbsp;Panli Ni ,&nbsp;Fabiao Yu ,&nbsp;Tongmeng Jiang ,&nbsp;Juan Wang","doi":"10.1016/j.jot.2024.09.011","DOIUrl":"10.1016/j.jot.2024.09.011","url":null,"abstract":"<div><div>Osteoarthritis (OA) is a degenerative disease that affects multiple cells and associated extracellular matrix (ECM). Chondrocytes and chondroextracellular matrix together constitute articular cartilage tissue. Any factors that affect the activity of chondrocytes and destroy the metabolic balance of the chondrocyte ECM will lead to the inability of articular cartilage to perform normal functions. The articular subchondral bone and articular cartilage must be coordinated to resist enough friction and mechanical stress, so the articular subchondral bone lesion will aggravate the articular cartilage defect and vice versa. Synoviocytes, including fibroblast-like synoviocytes (FLSs) and synovial macrophages at the joint, are also important factors that cause low-grade chronic progressive inflammation of OA. Regulation of phenotype transformation of synovial macrophages has become another possible target for the clinical treatment of OA. Ubiquitination and deubiquitination are the main post-translational protein modification pathways in the human body, which are widely involved in multiple signaling pathways and physiological processes. Naturally, they also play a very important regulatory role in the occurrence and development of OA. These effects are summarized in this review, including (A) regulating the aging and apoptosis of chondrocytes, FLSs and osteoblasts; (B) regulation of ECM degradation; (C) regulation of macrophage phenotypic transformation; (D) modulation of skeletal muscle and adipose tissues. Ubiquitination targeting drugs for OA treatment are also listed. Depending on the high efficiency of ubiquitination and deubiquitination, understanding OA-related ubiquitination pathways can help design more efficient drugs to treat OA and provide more potential targets for clinical treatment.</div><div>The Translational Potential of This Article.</div><div>In this paper, the ubiquitination-related pathways in osteoarthritis (OA), including aging, apoptosis and autophagy in chondrocytes, osteoblasts, FLSs and macrophages were investigated. In particular, several ubiquitination-related targets are expected to be effective approaches for OA clinical treatment. In addition, in the process of OA occurrence and development, the complex relationship between the local joint area and other tissues including skeletal muscle and adipose tissue is also discussed. These myokines and adipokines from musculoskeletal tissues are all expected to become efficient targets for OA treatment apart from the joint itself. In addition, those myokines secreted by cardiovascular tissues would show potential therapeutic effects as well. What if altering the contents for these ubiquitination-related targets in the serum through exercise will provide a new idea for OA therapy or prevent OA from deteriorating continuously?</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 156-166"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421803","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Porous metal materials for applications in orthopedic field: A review on mechanisms in bone healing","authors":"Yutong Ma ,&nbsp;Yi Wang ,&nbsp;Shuang Tong ,&nbsp;Yuehan Wang ,&nbsp;Zhuoya Wang ,&nbsp;Rongze Sui ,&nbsp;Ke Yang ,&nbsp;Frank Witte ,&nbsp;Shude Yang","doi":"10.1016/j.jot.2024.08.003","DOIUrl":"10.1016/j.jot.2024.08.003","url":null,"abstract":"<div><h3>Background</h3><div>Porous metal materials have been widely studied for applications in orthopedic field, owing to their excellent features and properties in bone healing. Porous metal materials with different compositions, manufacturing methods, and porosities have been developed. Whereas, the systematic mechanisms on how porous metal materials promote bone healing still remain unclear.</div></div><div><h3>Methods</h3><div>This review is concerned on the porous metal materials from three aspects with accounts of specific mechanisms, inflammatory regulation, angiogenesis and osteogenesis. We place great emphasis on different cells regulated by porous metal materials, including mesenchymal stem cells (MSCs), macrophages, endothelial cells (ECs), etc.</div></div><div><h3>Result</h3><div>The design of porous metal materials is diversified, with its varying pore sizes, porosity material types, modification methods and coatings help researchers create the most experimentally suitable and clinically effective scaffolds. Related signal pathways presented from different functions showed that porous metal materials could change the behavior of cells and the amount of cytokines, achieving good influence on osteogenesis.</div></div><div><h3>Conclusion</h3><div>This article summarizes the current progress achieved in the mechanism of porous metal materials promoting bone healing. By modulating the cellular behavior and physiological status of a spectrum of cellular constituents, such as macrophages, osteoblasts, and osteoclasts, porous metal materials are capable of activating different pathways and releasing regulatory factors, thus exerting pivotal influence on improving the bone healing effect.</div></div><div><h3>The translational potential of this article</h3><div>Porous metal materials play a vital role in the treatment of bone defects. Unfortunately, although an increasing number of studies have been concentrated on the effect of porous metal materials on osteogenesis-related cells, the comprehensive regulation of porous metal materials on the host cell functions during bone regeneration and the related intrinsic mechanisms remain unclear. This review summarizes different design methods for porous metal materials to fabricate the most suitable scaffolds for bone remodeling, and systematically reviews the corresponding mechanisms on inflammation, angiogenesis and osteogenesis of porous metal materials. This review can provide more theoretical framework and innovative optimization for the application of porous metal materials in orthopedics, dentistry, and other areas, thereby advancing their clinical utility and efficacy.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 135-155"},"PeriodicalIF":5.9,"publicationDate":"2024-10-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421802","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Unveiling the role of CXCL8/CXCR2 in intervertebral disc degeneration: A path to promising therapeutic strategies","authors":"Pengfei Xue ,&nbsp;Long Lv ,&nbsp;Lei Liu ,&nbsp;Yuzhu Xu ,&nbsp;Chonggang Zhou ,&nbsp;Yuntao Wang","doi":"10.1016/j.jot.2024.08.022","DOIUrl":"10.1016/j.jot.2024.08.022","url":null,"abstract":"<div><h3>Background</h3><div>Intervertebral disc degeneration(IVDD) is the primary etiology of low back pain and radicular pain. Recent studies have found that chemokines play a role in IVDD, but the underlying mechanism is largely unclear.</div></div><div><h3>Methods</h3><div>Bioinformatics analysis was employed to screen CXCL8 as the target gene. The expression levels of CXCL8 and CXCR2 were quantified using RT-qPCR, western blot(WB), immunohistochemistry(IHC), and enzyme-linked immuno-sorbent assay(ELISA). In the IVDD mouse model, X-ray images, Safranin O-fast green staining(SO-FG), IHC, and WB were conducted to assess the therapeutic effects of CXCL8 on IVDD. Reactive oxygen species (ROS) production, apoptosis of nucleus pulposus cells (NPCs), and the involvement of the NF-κB pathway were evaluated through WB, flow cytometry, immunofluorescence(IF), and Tunnel assay.</div></div><div><h3>Results</h3><div>In our study, we observed that CXCL8 emerged as one of the chemokines that were up-regulated in IVDD. The mitigation of extracellular matrix degradation (ECM) and the severity of IVDD were significantly achieved by neutralizing CXCL8 or its receptor CXCR2(SB225002, CXCR2 antagonist). The release of CXCL8 from infiltrated macrophages within intervertebral discs (IVDs) was predominantly observed upon stimulation. CXCL8 exerted its effects on NPCs by inducing apoptosis and ECM degradation through the activation of CXCR2. Specifically, the formation of the CXCL8/CXCR2 complex triggered the NF-κB signaling pathway, resulting in an abnormal increase in intracellular ROS levels and ultimately contributing to the development of IVDD.</div></div><div><h3>Conclusion</h3><div>Our findings suggest that macrophage-derived CXCL8 and subsequent CXCR2 signaling play crucial roles in mediating inflammation, oxidative stress, and apoptosis in IVDD. Targeting the CXCL8/CXCR2 axis may offer promising therapeutic strategies to ameliorate IVDD.</div></div><div><h3>The translational potential of this article</h3><div>This study indicates that CXCL8 can effectively exacerbate the excessive apoptosis and oxidative stress of NPCs through activating the NF-κB pathway. This study may provide new potential targets for preventing and reversing IVDD.</div></div>","PeriodicalId":16636,"journal":{"name":"Journal of Orthopaedic Translation","volume":"49 ","pages":"Pages 119-134"},"PeriodicalIF":5.9,"publicationDate":"2024-10-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142421808","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}